In chronic renal failure, phosphorus retention plays a major role in the development of secondary hyperparathyroidism and osteodystrophy. Bricker, N. S. et al., Archives of Internal Medicine, 123: 543-553 (1969); Rubini, M. E. et al., Archives of Internal Medicine, 124:663-669 (1969); Slatopolsky, E. et al., Journal of Clinical Investigation, 50: 492-499 (1971); Bricker, N. S., New England Journal of Medicine, 286: 1093-1099 (1972); Slatopolsky, E. S. et al., Kidney Int., 2: 147-151 (1972).
To prevent phosphorus retention, antacids are often used to bind dietary phosphorus and, thus, prevent its absorption. The process, referred to as phosphorus binding, appears to be a chemical reaction between dietary phosphorus and the cation present in the binder compound, resulting in the formation of insoluble and hence unabsorbable phosphate compounds, adsorption of phosphorus ions on the surface of binder particles, or a combination of both. The cation in some antacids is aluminum or calcium.
Presently-used antacids are, however, quite inefficient at binding phosphorus in vivo. For example, in a recent study by Ramirez, et al., it was noted that even though aluminum- or calcium-containing antacids were administered in large excess, they bound only 19-35 percent of dietary phosphorus. Ramirez, J. A., et al., Kidney Int., 30: 753-759 1986). Similar conclusions can be derived from data presented in earlier studies. Kirsner, J. B. Journal of Clinical Investigation, 22: 47-52 (1943); Clarkson, E. M. et al., Clinical Science, 43: 519-531 (1972); Cam, J. M. et al., Clinical Science and Molecular Medicine, 51: 407-414 (1976); Man, N. K. et al., Proceedings of the European Dialysis and Transplantation Association, 12: 245-55 (1975).
Antacids are also used widely, often in large quantities, for indigestion, heartburn or peptic ulcer disease. Despite their consumption in large amounts and often over long periods of time, however, phosphorus depletion is uncommon in these settings. This fact is additional evidence of the inefficiency of antacids as phosphorus binding agents.
The inefficiency of commonly used phosphorus binders creates a clinical dilemma: the dose of the binder must be increased to control hyperphosphatemia, but increased risk of toxicity of the binder results. This includes bone disease and aluminum dementia from aluminum-containing antacids and hypercalcemia and soft tissue calcification from calcium-containing antacids. These risks are particularly problematic in patients with chronic renal disease. It would be very useful to have a phosphorus binder available, which does not have the risks associated with ingestion of presently-available binders and which is more efficient in binding phosphorus and, thus, does not have to be consumed in the large quantities necessary, for example, when calcium carbonate-containing compositions are used. Such a phosphorus binder would be particularly valuable for administration to individuals with chronic renal failure, in whom phosphorus retention is a serious concern and the risk of toxicity from consumption of presently-available binders is greater than in individuals in whom kidney function is normal.